Field-based similarity forcing in energy minimization and molecular matching

Pac Symp Biocomput. 1999:415-25. doi: 10.1142/9789814447300_0041.

Abstract

A new field-based similarity forcing procedure for matching conformationally-flexible molecules is presented. The method extends earlier work on similarity matching of molecules based upon the program MIMIC, by directly coupling a similarity function to a molecular mechanics force field. In this way conformational energetics are fully accounted for in the similarity matching process. Simultaneous similarity/conformational searches can then be undertaken within a Monte Carlo or molecular dynamics framework. Here, a Monte Carlo approach is used to provide a simple example of two HIV-1 reverse transcriptase inhibitors, nevirapine and alpha APA, that illustrates the basic characteristics of the method and suggests areas for further investigation.

MeSH terms

  • Calorimetry
  • Drug Design*
  • HIV Reverse Transcriptase / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Monte Carlo Method
  • Nevirapine / chemistry*
  • Protein Conformation
  • Reverse Transcriptase Inhibitors / chemistry*
  • Software*
  • Static Electricity
  • Thermodynamics

Substances

  • Reverse Transcriptase Inhibitors
  • Nevirapine
  • HIV Reverse Transcriptase